A new study from Mass General Brigham reveals that targeting the TBK1 gene could enhance the effectiveness of CAR T-cell therapy for treating solid tumors. Researchers used a unique 3D tumor model to demonstrate that inhibiting TBK1 restored CAR T-cell function and increased their ability to destroy cancer cells.
Mass General Brigham researchers have discovered that inhibiting the TBK1 gene could enhance the effectiveness of CAR T-cell therapy for solid tumors . The study, published in Cancer Immunology Research, used a unique 3D model of tumors called patient-derived organotypic tumor spheroids (PDOTS) to investigate treatment resistance . Findings showed that CAR T-cells experienced dysfunction and reduced efficacy after encountering target cells, leading to an increase in inhibitory receptors.
However, inhibiting TBK1 restored CAR-T cell activity, prevented dysfunction, and increased T cell proliferation. Additionally, the study found that blocking TBK1 made cancer cells more vulnerable to immune cell targeting and destruction. These results suggest that targeting TBK1 could overcome treatment resistance and improve CAR T-cell therapy outcomes for solid tumors expressing B7-H3. The study also highlights the value of PDOTS as a model for studying tumor-immune interactions. The research was a collaboration between the Krantz Family Center for Cancer Research at Mass General Cancer Center and the late Soldano Ferrone's lab, completed with the continued support of his daughter, Cristina Ferrone, MD
CAR T-Cell Therapy Solid Tumors TBK1 Treatment Resistance Immunotherapy
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